title: Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide.
abstract: BACKGROUND
  Reduced expression of somatostatin receptors (SSTRs) in somatotroph adenomas and their potential down-regulation after medical treatment may explain the unsatisfactory response to octreotide in particular acromegalic patients. The expression of SSTRs other than SSTR2a has not been studied in large, unselected cohorts using novel rabbit monoclonal antibodies.
  
  
  OBJECTIVE
  We aimed to determine the expression of SSTRs 1, 2a, 3, and 5 in somatotroph adenomas, to correlate expression with clinical characteristics and the response to octreotide, and to ascertain whether preoperative octreotide treatment affected SSTR expression.
  
  
  METHODS
  The study included 78 adenomas from patients operated on consecutively during 2000 to 2010. After exclusion of 13 patients, immunohistochemical analysis with rabbit monoclonal antibodies against SSTRs 1, 2a, 3, and 5 (clones UMB-7, -1, -5, and -4) was performed on 65 adenomas.
  
  
  METHODS
  Twenty-eight patients received preoperative octreotide, and 37 patients were operated on without pretreatment. Twenty-six patients were randomized to direct surgery (n = 13) or to octreotide pretreatment (n = 13).
  
  
  METHODS
  SSTR expression was evaluated using a 12-grade scoring system. The responses to the octreotide test dose (GH reduction) and to 6 months of octreotide (IGF-I reduction) were measured.
  
  
  RESULTS
  The majority of adenomas showed membranous expression of SSTRs 2a and 5. SSTR2a expression was reduced in the pretreated group and correlated with the acute octreotide test results and the effect of octreotide treatment. In a linear regression model with SSTR2a expression as the determinant, the correlation with the acute test response improved after adjustment for medical pretreatment.
  
  
  CONCLUSIONS
  Rabbit monoclonal antibodies are reliable markers of SSTRs in somatotroph adenomas. SSTR2a expression correlated with the response to octreotide and was reduced after octreotide treatment, indicating the need for adjustment when SSTR2a expression is correlated with baseline characteristics. Evaluation of SSTR subtypes may be an important aspect of improving the medical treatment for acromegaly.
authors.affiliation: Section of Specialized Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway. ansgar.heck@medisin.uio.no.
authors.forename: Olivera
authors.initials: O
authors.lastname: Casar-Borota
authors.forename: Ansgar
authors.initials: A
authors.lastname: Heck
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Jahn Marthin
authors.initials: JM
authors.lastname: Nesland
authors.forename: Jon
authors.initials: J
authors.lastname: Ramm-Pettersen
authors.forename: Tove
authors.initials: T
authors.lastname: Lekva
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D011300:Preoperative Care / Q000379:methods; D011817:Rabbits; D017481:Receptors, Somatostatin / Q000276:immunology / Q000378:metabolism*; D013995:Time; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C101130:somatostatin receptor type 1; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D015282:Octreotide